Development of receptors for N-methylated lysine- and arginine-derivatives

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Within this project, we suggest the development of supramolecular receptors for a fluorescence-based detection of methylated lysine- and arginine-derivatives. The posttranslational modification (PTM) of lysine and arginine sidechains has an important function for the regulation and expression of genes, so that analytical tools for their detection and quantification would be of high value. The proposed receptors are especially designed for the detection of partially methylated Derivates (such as Kme, Kme2, Rme, sRme2), because no synthetic receptors have yet been developed for these PTMs.For the development of suitable receptors, we suggest a modular concept. First, suitable primary binding motifs will be synthesized based on BINOL-phosphates, allowing a selective interaction with the methylated amino- and guanidino-groups. BINOL-phosphates allow the interaction with these amino-acid sidechains based on several noncovalent interactions, most importantly hydrogen-bonding and cation-pi-interactions. These primary binding motifs will then be integrated into multidentate receptors, which possess additional secondary binding motifs. This is meant to give sufficient binding affinities, especially in an aqueous environment. The resulting receptors will subsequently be applied for the identification and quantification of methylated lysine- and arginine-derivatives. We will use a stepwise approach, starting with isolated amino acids, followed by short peptides and finally entire histone proteins.If successful, the newly developed receptors would allow a simple, fluorescence-based identification of partially methylated lysines and arginines for the first time, thus representing a valuable (bio)analytical tool.